Our view on organismal evolution is intimately connected to our understanding of how genomes and the encoded information change over time, and how this translates to the phenotypic and functional characteristics of contemporary species. The sequencing of entire genomes and transcriptomes from species covering all major groups in the tree of life has lifted the data basis for evolutionary research with a functional perspective to an unprecedented level. In its combination, this data facilitates access to the full repertoire of information stored in a species' genome and allows unraveling individual cellular programs translating genetic information into a diverse set of functions. However, the effort connected to the experimental functional characterization of even considerably few proteins in the lab is still enormous. It is for this reason that exhaustive functional studies are limited to few and well established model organisms, many of which are of economical or medical relevance. More often only individual pathways are studied in niche model organisms featuring a particular trait of interest. However, for the vast majority of species only a draft genome assembly or transcript data is available without further experimental support. In these instances the in silico prediction of genes together with a subsequent tentative transfer of functional annotation from corresponding sequences in experimentally characterized model organisms provides the only source of functional information. Integrating all available information into a comprehensive picture of organismal and functional evolution is the common denominator of the individual projects in our group.

We concentrate on the following main research topics:

1) Reconstructing the evolutionary histories of species and of their genes

We use phylogenomics approaches considering hundreds of genes across a similar number of species to reconstruct comprehensive phylogenies on different taxonomic levels. The resulting trees provide the scaffold for subsequently mapping information about the presence and absence of genes in large numbers of species considering both sequence homology and functional domain architecture.  

Example Publications 

• A consistent phylogenetic backbone for the fungi
• Tek (Tie2) is not required for cardiovascular development in zebrafish

2) Functional annotation transfer between homologous proteins

The transfer of functional annotations between biological sequences is a multi-layered procedure of which the most basic step is typically the identification of orthologs to functionally annotated proteins from model organisms in non-model organisms. Unfortunately, evolutionary relationships between proteins alone are only a poor proxy for functional equivalence. To ameliorate this problem, we aim at including additional evidences to achieve a more reliable annotation transfer by that minimizing the requirement of human curation. We are currently integrating an automated scoring of functional domain architecture similarities with the search for homologs. Moreover, we take the phylogenetic profiles of the respective proteins together with those of proteins interacting in the same functional pathway into account.

Example Publications

• FAS: assessing the similarity between proteins using multi-layered feature architectures
• A multi-level perspective on the evolution of orthologs and their functions

3) From phylogenetic profiles to the evolution of gene interaction networks

Phylogenetic profiles of proteins sharing the same function allow reconstructing when in evolutionary history individual gene interaction networks emerged, and help assessing their fate in individual phylogenetic lineages. This provides valuable insights into the direction of organismal evolution. Partial or complete losses of evolutionary old pathways indicate reductive evolution often associated with the change of an ancestral phenotype.

Example publications

• Tracing eukaryotic ribosome biogenesis factors into the archeal domain
• Genomic evidence for the widespread presence of GH45 cellulases among soil invertebrates

4) Evolution of species-specific phenotypes

We integrate phylogenomics tree reconstruction, feature architecture-aware phylogenetic profiling and functional inference to study how human pathogens emerge from their largely a-pathogenic ancestors. This sheds light on the molecular mechanisms of host-pathogen interaction and forms the basis of novel routes of treatment.

Example publications

• Feature architecture aware phylogenetic profiling indicates a functional diversification of type IVa pili in the nosocomial pathogen Acinetobacter baumannii
• Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumannii complex

5) Tools for for managing, exploring and analysing genome-scale data in a functional and evolutionary context

We are developing, improving and benchmarking software and workflows for biological sequence analysis in a functional and evolutionary context.

Example publications

• Feature architecture-aware ortholog search with fDOG reveals the distribution of plant cell wall-degrading enzymes across life
• nc-Ortho: efficient and reliable identification of miRNA ortholog